Effect of classic soft drink Coca-Cola as a solvent in the administration of tramadol and diazepam on biochemical and histological changes in liver and kidney

Keywords: hepatotoxicity, nephrotoxicity, histology, tramadol, diazepam, Coke.

Abstract

The objective of this study was to determine the biochemical and morphological changes in the liver and kidney as a result of the acute administration of tramadol and diazepam with classic soft drink Coca-Cola (Coke ).

Method: Thirty-six (36) adult male Wistar rats were divided into six groups: Group A-control (distilled water), Group B (Coke ), Group C (tramadol, 50 mg/kg), Group D (tramadol dissolved in Coke, 50 mg/kg), Group E (diazepam, 10 mg/kg) and Group F (diazepam dissolved in Coke 10 mg/kg). All administrations were done intraperitoneal. Twenty-four hours after administration, blood samples were collected via cardiac puncture for evaluation of the liver (Aspartate aminotransferase [AST] and Alanine aminotransferase [ALT]), kidney (urea and creatinine [CREA]) function and the organs were excised and processed for histopathological examination.

Result: A significantly increased in AST, creatinine and urea concentrations was observed in  Tramadol and Coke Groups compared to control (P<0.05), while diazepam had no significant effect on AST, ALT (P>0.05), though it caused a significant increase in urea and CREA (P<0.05). Dissolving the tramadol in Coke aggravated its hepatotoxicity and nephrotoxicity, while Coke had no significant effect on diazepam. Histological examination also corroborated the biochemical result.

Conclusion: The results showed that mixing drugs with Coke does not improve the toxicity of tramadol and has no significant effect on diazepam.

Downloads

Download data is not yet available.

References

Akanbi MI, Augustina G, Theophilus AB, Muritala M, Ajiboye AS.  Impact of Substance Abuse on Academic Performance among Adolescent Students of Colleges of Education in Kwara State. Nigeria. Journal of Education and Practice 2015; 6 (28): 108-112. Available from: https://eric.ed.gov/?id=EJ1081233.

Oluremi D.  Drug abuse among Nigerian adolescents: strategies for counseling. Journal of International Social Research.  2012; 5(20): 341-346. Available from: http://www.sosyalarastirmalar.com/cilt5/cilt5sayi20_pdf/faroe_oluremi.pdf

Balogun SK. Chronic intake of separate and combined alcohol and nicotine on body maintenance among albino rats. Journal of Human Ecology 2006; 19(1): 21-24. doi: https://doi.org/10.1080/09709274.2006.11905852.

Nnachi, RO.  Physiological and behavioral changes in living tissues. Advanced Psychology of Learning and Scientific Enquiries; 2007.                        

Bethesda MD (2012) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].): National Institute of Diabetes and Digestive and Kidney Diseases. U.S. National Library of Medicine, National Center for Biotechnology Information.  https://pubmed.ncbi.nlm.nih.gov/31643176/                

Degenhardt L, Grebely J, Stone J, Hickman M, Vickerman P, Marshall BDL, Bruneau J, Altice FL, Henderson G, Rahimi-Movaghar A, Larney S. Global patterns of opioid use and dependence: harms to populations, interventions, and future action. The Lancet 2019; V. 394 (10208): 1560-1579.  doi: 10.1016/S0140-6736(19)32229-9.

Abdulahi Z.  Drug abuse among youths: Strategies for school counseling. The Nigerian Society of Educational Psychologists 2009; 1: 131-136.

Mattoo SK, Nebhinan N, Kumar BN, Basu D, Kulhara P. Family burden with substance dependence: a study from India. Indian Journal of Medical Resources 2013; 137: 704-711. Availiable from: https://pubmed.ncbi.nlm.nih.gov/23703337/

Faria J, Barbosa J, Leal S, Afonso LP, Lobo J, Moreira R, Queiros O, Carvalho F, Dinis Oliveira RJ.  Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in wistar rats. Toxicology 2017; 385: 38–47. doi: 10.1016/j.tox.2017.05.003.

Ryan NM, Isbister GK. Tramadol overdose causes seizures and respiratory depression but serotonin toxicity appears unlikely. Clin. Toxicol 2015; 53 (6) : 545–550. doi: 10.3109/15563650.2015.1036279.

Souza MJ, Martin-Jimenez T, Jones MP, Cox SK. Pharmacokinetics of oral tramadol in red-tailed hawks (Buteo jamaicensis). Veterinary Pharmacology Therapy 2011; 34: 86-88. doi: 10.1111/j.1365-2885.2010.01211.x. 

Badawi SM, Hammad SA, Amin SA, Zanatya AAW, Aiad HA, Mohamed RH. Biochemical, histopathological, and immune-histochemical changes on the liver of adult albino rats due to dependence on tramadol, diazepam, and their combination. Menoufia Medical Journal 2016; 29:1122–1129. doi: 10.4103/1110-2098.202526.

Leppert W.  CYP2D6 in the metabolism of opioids for mild to moderate pain. Pharmacology 87, 274–285. doi: 10.1159/000326085.

Abdelmajeed N.  Diazepam-induced oxidative stress in rat different organs. Research Journal of Medical Science 2009; 4: 295-302. Availiable from: http://arnmsmb.com/old/rjmms/rjmms/2009/295-302.pdf

El-Sokkary GH. Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats: Melatonin, vitamin C and diazepam. Cell Proliferation 2008; 41(1): 168–176. doi: 10.1111/j.1365-2184.2007.00503.x  

Sakai M, Fonseca ESM, Dagli MLZ, Palermo-Neto J. Diazepam effects on Ehrlich tumor growth and macrophage activity in mice. Life Sciences 2006; 78 (16):1777-1783  doi: https://doi.org/10.1016/j.lfs.2005.08.015.

Bronstein AC, Spyker DA, Cantilena LR, Green JL, Rumack BH, Giffin SL. 2008 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS). 26th Annual Report on Clinical Toxicology (Philadelphia) 2009; 47: 911-1084. doi: https://doi.org/10.3109/15563650903438566.

Lagard C, Chevillard L, Malissin I,  Risède P, Callebert, Labat L, Launay J, Laplanche J,     Mégarbane B. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose? Toxicology and Applied Pharmacology 2016; 310: 108–119. doi: 10.1016/j.taap.2016.09.013.

Tarek MM, Hamdy MAG, Rabee MRE.  Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes. Toxicology and Industrial Health 2013; 1–9.  doi: 10.1177/0748233713491814.

Jyothi TM.  Health risks of soft drinks-a review. Asian Journal of Science and Technology 2016; 7 (6) : 3059-3064. Available from: https://www.journalajst.com/sites/default/files/issues-pdf/3098.pdf

Mueller NT, Jacobs DR Jr, MacLehose RF, Demerath EW, Kelly SP, Dreyfus JG, Pereira MA.  Consumption of caffeinated and artificially sweetened soft drinks is associated with risk of early menarche. Am J Clin Nutr 2015; 102 (3):648-54. doi: 10.3945/ajcn.114.100958.

Fitzgerald RL. Disposition of Toxic Drugs and Chemicals in Man, 8th Edition. Randall C. Baselt. Foster City, CA: Biomedical Publications; 2009. doi: 10.1373/clinchem.2009.133827

Oiestad EL, Johansen U, Oiestad AML, Christophersen AS. Drug screening of whole blood by ultra-performance liquid chromatography-tandem mass spectrometry. J Anal Toxicol 2011; 35:280–93. doi: 10.1093/anatox/35.5.280/.

Ohshima T. A case of drug-facilitated sexual assault by the use of flunitrazepam. Journal of Clinical Forensic Medicine 2006; 13: 44–45. doi: https://doi.org/10.1016/j.jcfm.2005.05.006.

Atici S, Cinel I, Cinel L, Doruk N, Eskandari G & Oral U. Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J Biosci 2005; 30:245–252. doi: 10.1007/BF02703705.

Samarghandian S, Afshari R, Farkhondeh T.  Effect of long-term treatment of morphine on enzymes, oxidative stress indices and antioxidant status in male rat liver. Int J Clin Exp Med 2014; 7(5):1449-1453. Available from: http://www.ijcem.com/files/ijcem0000404.pdf.

Stevens A, Wilson IG. The haematoxylin and eosin. In: Bancroft JD, Stevens A, Turner DR, editors. Theory and practice of histological techniques. 4th ed. New York: Churchill Livingstone 1996: 99–112.

Øiestad EL, Karinen R, Asbjørg S. Christophersen AS, Vindenes V, and Bachs L. Analyses of Beverage Remains in Drug Rape Cases Revealing Drug Residues- The Possibility of Contamination from Drug Concentrated Oral Fluid or Oral Cavity Contained Tablets. J Forensic Sci, 2014; 59 (1): 208-211. doi: https://doi.org/10.1111/1556-4029.12270.

Ferdousy S, Rahman A, Al-Amin M, Aklima J & Chowdhury JMKH. Antioxidative and neuroprotective effects of Leea macrophylla methanol root extracts on diazepam-induced memory impairment in amnesic Wistar albino rat. Clinical Phytoscience 2016; 2 (17):1-11. Available from: https://clinphytoscience.springeropen.com/articles/10.1186/s40816-016-0031-6

Liu ZM, Zhou WH, Lian Z, Mu Y, Ren ZH, Cao JQ, Cai ZJ. Drug dependence and abuse potential of tramadol. Acta Pharmacologica Sinica 1999; 20(1):52-54. Availiable from: https://pubmed.ncbi.nlm.nih.gov/10437125/.

Bruckauf Z, Walsh SD.  Adolescents’ multiple and individual risk behaviors: examining the link with excessive sugar consumption across 26 industrialized countries. Soc Sci Med. 2018; 216:133–141. doi: 10.1016/j.socscimed.2018.08.029.

Pan X, Zhang C, Shi Z.  Soft drink and sweet food consumption and suicidal behaviors among Chinese adolescents. Acta Paediatr 2011; 100 (11): 215–22. doi: 10.1111/j.1651-2227.2011.02369.x.

Ziegler AM, Temple JL. Soda consumption is associated with risk-taking behaviors in adolescents. Am J Health Behav 2015; 9(6):761–771. doi: 10.5993/AJHB.39.6.3

Ugwu N, Eze C, Udegbunam R. Evaluation of haematological and serum biochemical changes associated with constant rate infusion tramadol hydrochloride as an adjunct to ketoprofen in laparotomized and ovariohysterectomized dogs. Comparative Clinical Pathology 2017; 26 (5): 1135-1140. doi: 10.1007/s00580-017-2498-z.

Kaoud HA, Hellal MH, Malhat FM, Saeid S, Elmawella IA, Khalil AH. Effects of acute sub‑lethal dose of tramadol on α2‑adrenergic receptors and liver histopathology in rat. Global J Curr Res 2013; 1:70–76. Available from:  http://www.crdeepjournal.org/wp-content/uploads/2013/03/Vol-1-2-5-GJCR.pdf.

Kondal A, Garg SK. Influence of acidic beverage (Coca-Cola) on pharmacokinetics of ibuprofen in healthy rabbits. Indian J Exp Biol. 2003;41(11):1322-1324.

Larrey D, Ripault MP.  Hepatotoxicity of Psychotropic Drugs and Drugs of Abuse. Drug-Induced Liver Disease 2013; 25: 443–462. doi:10.1016/b978-0-12-387817-5.00025-x

Lugoboni F., Antonio Mirijello, Laura Morbioli, Elena Arzenton, Roberto Leone, Marco Faccini, Rebecca Casari, Salvatore De Cosmo, Antonio Gasbarrini & Giovanni Addolorato. Does high-dose benzodiazepine abuse really produce liver toxicity? Results from a series of 201 benzodiazepine monoabusers 2018;17(5):451-456. doi: 10.1080/14740338.2018.1457646.

Mudd E. Interaction of caffeine with benzodiazepines: behavioural effects in mice. Pharmacological Sciences 2012; 12(2): 1-12.

Miners JO, Yang X, Knights KM, Zhang L. The Role of the Kidney in Drug Elimination: Transport, Metabolism and the Impact of Kidney Disease on Drug Clearance. Clin Pharmacol Ther.  2017; 102(3):436-449. doi: 10.1002/cpt.757.   

Agarwal D, Elks CM, Reed SD, Mariappan N, Majid DS, Francis J. Chronic exercise preserves renal structure and hemodynamics in spontaneously hypertensive rats. Antioxid Redox Signal. 2012; 16: 139–152. doi: 10.1089/ars.2011.3967 PMID: 21895524.

Tothova LU, Hodosy J, Mettenburg K, Fabryova H, Wagnerova A, Babicˇkova J, Okuliarova M, Zeman M, Celec P. No harmful effect of different Coca-cola beverages after 6 months of intake on rat testes. Food and Chemical Toxicology 2013; 62: 343–348. doi: 10.1016/j.fct.2013.08.073.

Crowe, A.V., Howse M., Bell G.M.  & Henry J.A. Substance abuse and the kidney. International Journal of Medicine 2000; 93:147–152. doi.org/10.1093/qjmed/93.3.147.

Howse, M. L. P, & G. M Bell. Drugs and toxins that damage the kidney. Drugs and the Kidney. Medicine 2011; 39 (6): 356-361. 

Pereira MP, Gomes de Gomes M, Izoton JC, Nakama KA et al.  "Cationic and anionic unloaded polymeric nanocapsules: Toxicological evaluation in rats shows low toxicity", Biomedicine Pharmacotherapy;  2019.

Griffin III, Charles E., A. M. Kaye, F. R. Bueno & A. D. Kaye. Benzodiazepine Pharmacology and Central Nervous System Mediated Effects. The Ochsner Journal. 2013; 13:214–223.

Samaka, R, Girgis N,  Shams T.  Acute toxicity and dependence of tramadol in albino rats: relationship of nestin and notch 1 as stem cell markers. Journal of Am Science 2012; 88(6): 313-327.

Akinpelu M, Ikechi GE, Ronald AB, Ogbonnaya AA, Michael CI.  Evaluation of herbal cocktail used in the treatment of malaria on liver tissue of adult Wistar rats. Journal of Medicinal Plants Research 2018; 12(28):508-521. doi: 10.5897/JMPR2018.6661.

Cao G., González J., Müller A., Ottaviano G., Ambrosio G., Toblli J. E., Milei J.  Beneficial Effect of Moderate Exercise in Kidney of Rat after Chronic Consumption of Cola Drinks,   PLOS ONE 2016; 11(3):e0152461.  doi.org/10.1371/journal.pone.0152461.

Godoy JR, Oesteritz S, Hanschmann EM, Ockenga W, Ackermann W, Lillig CH.  Segment-specific overexpression of redoxins after renal ischemia and reperfusion: protective roles of glutaredoxin 2, peroxiredoxin 3, and peroxiredoxin 6. Free Radic Biol Med. 2011; 51: 552–561. doi: 10.1016/j. freeradbiomed.2011.04.036.

Mei W, Peng Z, Lu M, Liu C, Deng Z, Xiao Y, et al. (2015) Peroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal tubulointerstitial fibrosis. Nephrology (Carlton) 2015; 20 (11):832-842    doi: 10.1111/nep. 12515.

Otero-Losada ME, Grana DR, Müller A, Ottaviano G, Ambrosio G, Milei J.  Lipid profile and plasma antioxidant status in sweet carbonated beverage-induced metabolic syndrome in rat. Int J Cardiol. 2010; 146: 106–109. doi: 10.1016/j.ijcard.2010.09.066.


Abstract views: 737
PDF Downloads: 112
Published
2020-05-20
How to Cite
Ilesanmi, O. B., & Odewale, T. T. (2020). Effect of classic soft drink Coca-Cola as a solvent in the administration of tramadol and diazepam on biochemical and histological changes in liver and kidney. Ukrainian Journal of Nephrology and Dialysis, (3(67), 33-41. https://doi.org/10.31450/ukrjnd.3(67).2020.06